Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 G2032R and ALK G1202R

doi: 10.1080/14756366.2023.2227779

Figure Lengend Snippet: Structures of representative ROS1/ALK dual inhibitors.

Article Snippet: Kinase inhibitory detection for ROS1, ALK WT , ALK G1202R , and ALK L1196M (Carna Biosciences, lot: 10CBS-0385B for ROS1; 13CBS-0537B for ALK) were performed with the HTRF KinEASE-TK assay from Cisbio according to the manufacturer’s instructions.

Techniques:

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 G2032R and ALK G1202R

doi: 10.1080/14756366.2023.2227779

Figure Lengend Snippet: Design strategies of target compounds based on cocrystal structures of Crizotinib with ROS1 WT (PDB 3ZBF) and ALK WT (PDB 2XP2). (A ) Docking structure of Crizotinib binding to apo-G2032R ROS1 receptor. (B) Docking structure of Crizotinib binding to apo-G1202R ALK receptor. (C) 2D structure of Crizotinib. (D) Docking posture of Crizotinib binding to ROS1 receptor. (E) Design strategies for novel 2-aminopyridine analogues as ROS1/ALK dual inhibitors. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article).

Article Snippet: Kinase inhibitory detection for ROS1, ALK WT , ALK G1202R , and ALK L1196M (Carna Biosciences, lot: 10CBS-0385B for ROS1; 13CBS-0537B for ALK) were performed with the HTRF KinEASE-TK assay from Cisbio according to the manufacturer’s instructions.

Techniques: Binding Assay, Analogues

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 G2032R and ALK G1202R

doi: 10.1080/14756366.2023.2227779

Figure Lengend Snippet: In vitro activities against Crizotinib-resistant ROS1 G2032R and ALK G1202R mutants. Dose–response curves for proliferation of Ba/F3 CD74-ROS1 WT cell (A), Ba/F3 CD74-ROS1 L2026M cell (B), Ba/F3 CD74-ROS1 G2032R cell (C), Ba/F3 EML4-ALK WT cell (D) and Ba/F3 EML4-ALK L1196M cell (E) after 72 h exposure to B08 , C01–C03 , and Crizotinib. (F) Enzyme-based activities of B08 , C01, C02 , and Crizotinib against ALK G1202R mutant. All data are the average of n ≥ 2 ± standard deviation.

Article Snippet: Kinase inhibitory detection for ROS1, ALK WT , ALK G1202R , and ALK L1196M (Carna Biosciences, lot: 10CBS-0385B for ROS1; 13CBS-0537B for ALK) were performed with the HTRF KinEASE-TK assay from Cisbio according to the manufacturer’s instructions.

Techniques: In Vitro, Mutagenesis, Standard Deviation

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 G2032R and ALK G1202R

doi: 10.1080/14756366.2023.2227779

Figure Lengend Snippet: Enzymatic and cellular activities to ROS1 and ALK mutants.

Article Snippet: Kinase inhibitory detection for ROS1, ALK WT , ALK G1202R , and ALK L1196M (Carna Biosciences, lot: 10CBS-0385B for ROS1; 13CBS-0537B for ALK) were performed with the HTRF KinEASE-TK assay from Cisbio according to the manufacturer’s instructions.

Techniques:

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 G2032R and ALK G1202R

doi: 10.1080/14756366.2023.2227779

Figure Lengend Snippet: Inhibition of cellular phosphorylation of ROS1, ALK, and ERK by C01 in CD74-ROS1 WT (A), CD74-ROS1 L2026M (B), CD74-ROS1 G2032R (C), and EML4-ALK L1196M (D) cells investigated by western blot analysis, with Crizotinib as the positive control. Cells were treated with Crizotinib or C01 at the indicated concentrations for 4 h and the levels of protein were evaluated by western blot analysis of cell lysates using specific antibodies.

Article Snippet: Kinase inhibitory detection for ROS1, ALK WT , ALK G1202R , and ALK L1196M (Carna Biosciences, lot: 10CBS-0385B for ROS1; 13CBS-0537B for ALK) were performed with the HTRF KinEASE-TK assay from Cisbio according to the manufacturer’s instructions.

Techniques: Inhibition, Western Blot, Positive Control

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 G2032R and ALK G1202R

doi: 10.1080/14756366.2023.2227779

Figure Lengend Snippet: Representative structures from MD simulation of C01 (A) and Crizotinib (B) in the active site of ROS1 G2032R . (ROS1 in coloured cartoon, ligands, and residues in stick mode. Yellow dots represent hydrogen bonds). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.) (C) 2D diagram of the interaction between C01 and the binding site of ROS1 G2032R . (D) 2D diagram of the interaction between Crizotinib and the binding site of ROS1 G2032R .

Article Snippet: Kinase inhibitory detection for ROS1, ALK WT , ALK G1202R , and ALK L1196M (Carna Biosciences, lot: 10CBS-0385B for ROS1; 13CBS-0537B for ALK) were performed with the HTRF KinEASE-TK assay from Cisbio according to the manufacturer’s instructions.

Techniques: Binding Assay

Journal: Frontiers in Physiology

Article Title: High Glucose Attenuates Cardioprotective Effects of Glucagon-Like Peptide-1 Through Induction of Mitochondria Dysfunction via Inhibition of β-Arrestin-Signaling

doi: 10.3389/fphys.2021.648399

Figure Lengend Snippet: Catalog numbers of commercially available kits and agents.

Article Snippet: ROS assay kit , Abcam, United Kingdom , ab113851.

Techniques: TUNEL Assay, Caspase-3 Assay, ROS Assay, CCK-8 Assay